Consequence of the presence of two different β subunit isoforms in a GABAA receptor

• Published in: Journal of neurochemistry 2005-12, Vol.95 (6), p.1724-1731
• Main Authors: Boulineau, Nathalie, Baur, Roland, Minier, Frédéric, Sigel, Erwin
• Format: Article
• Language: English
• Subjects: Aminoacid receptors (glycine, glutamate, gaba); Biological and medical sciences; Cell receptors; Cell structures and functions; etomidate; Fundamental and applied biological sciences. Psychology; GABA; GABAA receptors; loreclezole; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); β subunit isoforms
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03495.x

The major isoforms of GABAA receptors are thought to be composed of two α, two β and one γ subunit(s). GABAA receptors containing two β1 subunits respond differently to the anticonvulsive compound loreclezole and the general anaesthetic etomidate than receptors containing two β2 subunits. Receptors containing β2 subunits show a much larger allosteric stimulation by these agents than those containing β1 subunits. We were interested to know how receptors containing both β1 and β2 subunits, in different positions respond to loreclezole and etomidate. To answer this question, subunits were fused at the DNA level to form dimeric and trimeric subunits. Concatenated receptors (α1‐β1‐α1/γ2‐β1, α1‐β2‐α1/γ2‐β1, α1‐β1‐α1/γ2‐β2 and α1‐β2‐α1/γ2‐β2) were expressed in Xenopus ooctyes and functionally compared in their response to the agonist GABA and to the positive allosteric modulators, loreclezole and etomidate. We have shown that (I) in the presence of both β1 and β2 subunits in the same pentamer (mixed receptors) direct gating by etomidate is similar to exclusively β1 containing receptors; (II) In mixed receptors, stimulation by etomidate assumed characteristics intermediate to exclusively β1 or β2 containing receptors, but the values for the concentrations < 10 µm were always much closer to those observed in α1‐β1‐α1/γ2‐β1 receptors; and (III) mixed receptors show no positional effects.